Value of perfusion parameters from golden-angle radial sparse parallel dynamic contrast-enhanced magnetic resonance imaging in predicting pathological complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

PURPOSE: Non-invasive methods for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) can provide distinct leverage in the management of patients with locally advanced rectal cancer (LARC). This study aimed to investigate whether including the golden-angle radial sparse parallel (GRASP) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion parameter (Ktrans), in addition to tumor regression grading (TRG) and apparent diffusion coefficient (ADC) values, can improve the predictive ability for pCR. METHODS: Patients with LARC who underwent nCRT and subsequent surgery were included. The imaging parameters were compared between patients with and without pCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of these parameters for pCR. RESULTS: A total of 111 patients were included in the study. A pCR was obtained in 32 patients (28.8%). MRI-based TRG (mrTRG) showed a negative correlation with pCR (r = -0.61, P < 0.001), and the average ADC value showed a positive correlation with pCR (r = 0.62, P < 0.001). Before nCRT, Ktrans in the pCR group was significantly higher than in the non-pCR group (1.30 ± 0.24 vs. 0.88 ± 0.34, P < 0.001), but no difference was identified after nCRT. Following ROC curve analysis, the area under the curve (AUC) of mrTRG (level 1-2), average ADC value, and Ktrans value for predicting pCR were 0.738 [95% confidence interval (CI): 0.65-0.82], 0.78 (95% CI: 0.69-0.86), and 0.84 (95% CI: 0.77-0.92), respectively. The model combining the three parameters had significantly higher predictive ability for pCR (AUC: 0.94, 95% CI: 0.88-0.98). CONCLUSION: The use of a combination of the GRASP DCE-MRI Ktrans with mrTRG and ADC can lead to a better pCR predictive performance.

The Effect of Induction Chemotherapy with VEGF Inhibition on Tumor Response in Synchronously Metastasized Potentially Resectable Colorectal Cancer.

(1) Background: The pathological tumor response of the primary tumor to induction chemotherapy in synchronously metastasized colorectal cancer (mCRC) patients has not been investigated. The aim of this study was to compare patients treated with induction chemotherapy combined with vascular endothelial growth factor (VEGF) or with epidermal growth factor receptor (EGFR) antibodies. (2) Methods: We present a retrospective analysis, where we included 60 consecutive patients with potentially resectable synchronous mCRC who received induction chemotherapy combined with either VEGF or EGFR antibodies. The primary endpoint of this study was the regression of the primary tumor, which was assessed by the application of the histological regression score according to Rödel. The secondary endpoints were recurrence-free survival (RFS) and overall survival (OS). (3) Results: A significantly better pathological response and a longer RFS for patients treated with the VEGF antibody therapy compared to those treated with the EGFR antibodies was demonstrated (p = 0.005 for the primary tumor and log-rank = 0.047 for RFS). The overall survival did not differ. The trial was registered with clinicaltrial.gov, number NCT05172635. (4) Conclusion: Induction chemotherapy combined with a VEGF antibody revealed a better pathological response of the primary tumor, leading to a better RFS compared to that with EGFR therapy; this has clinical relevance in patients with potentially resectable synchronously mCRC.

Does neoadjuvant rectal score predict treatment outcomes better than the all grading systems used in neoadjuvantly treated rectal cancer?

BACKGROUND: /Objective: To compare the prognostic value of the yield pathologic (yp) stage, used 4 tumor regression grading (TRG) systems, and neoadjuvant rectal score(NARS) in patients with locally advanced rectal cancer (LARC) who received long-term neoadjuvant chemoradiotherapy (nCRT). METHODS: Between 2005 and 2017, we included 302 patients with LARC who treated with nCRT. Postoperative pathological responses were graded by using Dworak, American Joint Committee on Cancer, Mandart, Memorial Sloan Kettering Cancer Center, grading systems and NARS([5ypN-3(kT-pT)+12]2/9,61) calculations. Their results were compared in terms of treatment outcomes. RESULTS: The median follow-up time was 51 months (range 5-136). There was a significant relation between cT stage and the response in used grading systems(p < 0,001). Median overall(OS), local recurrence free(LRFS), and distant metastasis free(MFS) survival rates were 50, 48, and 45 months, respectively. 5-year OS, LRFS, and MFS rates were 71%, 92%, and 72%, respectively. According to the NARS and treatment response grating systems, a significant difference was found between the low risk and high risk groups in terms of OS, LRFS, and MFS rates. While it was not seen any difference in terms of OS and MFS, NARS was found to predict LRFS better than other grading systems. In multivariate analysis, high NARS was found to be correlated with worse OS and worse MFS. On the other hand, pCR was the another important factor affecting treatment outcomes. CONCLUSIONS: While used systems except NARS group patients according to ypT status in surgical tissue, NARS add the value of ypN status in addition to ypT status. It could be suggested to use NARS to predict LRFS.

Pathologic assessment of esophageal cancer following neoadjuvant therapy / 中国胸心血管外科临床杂志

@#China is a country with a high incidence of esophageal cancer. Most patients are already in the locally advanced stage when first diagnosed. Preoperative neoadjuvant therapy followed by surgery has become the standard treatment mode for them. Closely related to prognosis, the evaluation of tumor response is essential. Response evaluation criteria in solid tumors is the gold standard to evaluate tumor response, but the lesions must meet the measurement standards. Tumor regression grading (TRG) systems are designed to classify regressive changes after neoadjuvant treatment based on histopathological results to reveal prognostic information. Concentrating on pathologic assessment of esophageal cancer following neoadjuvant therapy, this article reviews histopathological changes, commonly used TRG systems and current debate.

Can patients with good tumor regression grading after neoadjuvant chemoradiotherapy be exempted from lateral lymph node dissection?

OBJECTIVE: To investigate whether lateral lymph node (LLN) dissection (LLND) can be exempted in patients with good tumor regression grading (TRG) after neoadjuvant chemoradiotherapy (nCRT)? METHODS: A retrospective study was conducted on consecutive patients with advanced rectal cancer who underwent nCRT and total mesorectal resection plus selective LLND at our institution. The primary outcomes are the relationship between LLN metastasis (LLNM) and magnetic resonance imaging TRG (mrTRG) and the relationship between LLNM and pathological TRG (pTRG). RESULTS: A total of 91 patients were included, of which 24 patients (26.4%) had LLNM, 67 patients (73.6%) had no LLNM. There were significant differences of the maximum short-axis of LLN before and after nCRT, short-axis reduction rate of the LLN with maximum short-axis, length diameter reduction rate of primary tumor, mrTRG, and pTRG between the two groups. Multivariate logistic regression showed that mrTRG (P = 0.026) and pTRG (P = 0.013) were independent predictors for LLNM. The combination used by mrTRG and the maximum short-axis of LLNs ≥ 8 mm before nCRT and the maximum short-axis of LLN ≥ 5 mm after nCRT achieved specificity of 0.970, positive predictive value (PPV) of 0.867, and negative predictive value (NPV) of 0.855. The same combination used by pTRG achieved the specificity of 0.970, PPV of 0.857 and NPV of 0.844. CONCLUSION: The suspected positive LLNs tend to be sterilized by nCRT in patients who have a very good response to nCRT. It is rational to avoid LLND in patients whose primary tumor and LLNs both show good response to nCRT.

ACO/ARO/AIO-21 - Capecitabine-based chemoradiotherapy in combination with the IL-1 receptor antagonist anakinra for rectal cancer Patients: A phase I trial of the German rectal cancer study group.

Purpose: Recent advances in the treatment algorithm of locally advanced rectal cancer (LARC) have significantly improved complete response (CR) rates and disease-free survival (DFS), but therapy resistance, with its substantial impact on outcomes and survival, remains a major challenge. Our group has recently unraveled a critical role of interleukin-1α (IL-1α) signaling in activating inflammatory cancer-associated fibroblasts (iCAFs) and mediating radiation-induced senescence, extracellular matrix (ECM) accumulation, and ultimately therapy resistance. We here summarize the recently initiated ACO/ARO/AIO-21 phase I trial, testing the IL-1 receptor antagonist (IL-1 RA) anakinra in combination with fluoropyrimidine-based chemoradiotherapy (CRT) for advanced rectal cancer. Methods/Design: The ACO/ARO/AIO-21 is an investigator-driven, prospective, open-labeled phase I drug-repurposing trial assessing the maximum tolerated dose (MTD) of capecitabine administered concurrently to standard preoperative radiotherapy (45 Gy in 25 fractions followed by 9 Gy boost in 5 fractions) in combination with fixed doses of the IL1-RA anakinra (100 mg, days -10 to 30). Capecitabine will be administered using a 3 + 3 dose-escalation design (500 mg/m2 bid; 650 mg/m2 bid; 825 mg/m2 bid, respectively) from day 1 to day 30. Response assessment including digital rectal examination (DRE), endoscopy and pelvic magnetic resonance imaging (MRI) is scheduled 10 weeks after completion of CRT. For patients achieving clinical complete response (cCR), primary non-operative management is provided. In case of non-cCR immediate total mesorectal excision (TME) will be performed. Primary endpoint of this phase I trial is the MTD of capecitabine. Discussion: Based on extensive preclinical research, the ACO/ARO/AIO-21 phase I trial will assess whether the IL-1RA anakinra can be safely combined with fluoropyrimidine-based CRT in rectal cancer. It will further explore the potential of IL-1 inhibition to overcome therapy resistance and improve response rates. A comprehensive translational research program will expand our understanding from a clinical perspective and may help translate the results into a randomized phase II trial.

Completion of FLOT Therapy, Regardless of Tumor Regression, Significantly Improves Overall Survival in Patients with Esophageal Adenocarcinoma.

Esophageal cancer is the eighth most common cancer worldwide, with poor prognosis and high mortality. The combination of surgery and systemic therapy provide the best chances for long-term survival. The purpose of this study was to analyze the impact of the FLOT protocol on the overall survival of patients following surgery for esophageal adenocarcinoma, with a focus on the patients who did not benefit in terms of pathological remission from the neoadjuvant therapy. A retrospective analysis of all the patients who underwent esophagectomies from 2012 to 2017 for locally advanced adenocarcinomas of the esophagus at a tertiary medical center was performed. The results show that the completion of systemic therapy, regardless of the tumor regression grading, had a significant positive impact on the overall survival. The patients with complete regression and complete systemic therapy showed the best outcomes. Anastomotic insufficiency did not negatively impact the long-term survival, while complications of the systemic therapy led to significantly reduced overall survival. We conclude that adjuvant systemic therapy should, when possible, always be completed, regardless of the tumor regression, following an esophagectomy.

Assessing Post-Treatment Pathologic Tumor Response in Female Genital Tract Carcinomas: An Update.

In the last decades, several new therapeutic strategies have been introduced in the field of gynecologic oncology. These include neoadjuvant chemotherapy for high-grade serous tubo-ovarian carcinoma, hormonal fertility-sparing strategies for endometrial cancer, pressurized intraperitoneal aerosol chemotherapy (PIPAC) for surgically incurable peritoneal metastasis, and neoadjuvant treatments for locally advanced cervical carcinomas. All these recent advances lead to the development of novel scoring systems for the evaluation of pathological response related to specific treatments. In this regard, pathological evaluation of the morphological modifications related to these treatments and the definition of a tumor regression grading score have been introduced in clinical practice in order to achieve a more efficient prognostic stratification of patients affected by gynecological malignancies. The aim of the present paper is to provide a detailed review on the post-treatment pathological scoring systems in patients affected by gynecological malignancies.

Evaluation of the histopathologic status of rectal adenocarcinoma and its regional lymph nodes after neoadjuvant therapy, and its relation to the duration of disease-free survival.

INTRODUCTION: Colorectal cancer is one of the most common malignant tumors and has a relatively poor prognosis. Lymph node involvement is considered the most important prognostic factor. MATERIALS AND METHODS: During a retrospective cohort study, 132 patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy followed by surgery for resectable rectal cancer from 2010 to 2015 in Sina hospital were reviewed. RESULTS: Multivariable analysis was performed and shown the clinical stage was not a representative factor for disease-free survival (P = 0.187), but Dworak Tumor Regression Grading were significantly associated with higher disease-free survival (P = 0.000) in stage II and stage III. The total number of retrieved lymph nodes and involved lymph nodes in the same clinical stage were statistically associated with higher mean disease-free survival in patients (P = 0.000 in both conditions). CONCLUSION: In the same clinical stage, increasing the Dworak Tumor Regression Grading reduced the risk of rectal cancer recurrence. Increasing total number of retrieved lymph nodes and involved lymph nodes, 2.14 times and 3.87 times increased the risk of recurrence, respectively.

Four-Tier Pathologic Tumor Regression Grading System Predicts the Clinical Outcome in Patients Who Undergo Surgical Resection for Locally Advanced Pancreatic Cancer after Neoadjuvant Chemotherapy.

BACKGROUND/AIMS: Neoadjuvant chemotherapy is increasingly utilized in patients with borderline or locally advanced pancreatic cancer (LAPC). However, the pathologic evaluation of tumor regression is not routinely performed or well established. We aimed to evaluate the prognostic value of three tumor regression grading systems frequently used in LAPC and to determine the correlation between pathologic and clinical response. METHODS: We included a total of 38 patients with LAPC who were treated with neoadjuvant chemotherapy and subsequent resection. Pathologic tumor regression was graded based on the College of American Pathologists (CAP), Evans, and MD Anderson grading systems. RESULTS: One out of 38 patients (2.6%) achieved a pathologic complete response. Unlike other grading systems (Evans, p=0.063; MD Anderson, p=0.110), the CAP grading system was a significant prognostic factor for overall survival (p=0.043). Pathologic N stage (p=0.023), margin status (p=0.044), and radiologic response (p=0.016) correlated with overall survival. In the multivariate analysis, CAP 3 was an independent predictor of shorter overall survival (p=0.026). The CAP grading system correlated with the radiologic response (p=0.007) but not the carbohydrate antigen 19-9 level (p=0.333). CONCLUSIONS: The four-tier CAP pathologic tumor regression grading system predicted the clinical outcome in LAPC patients who underwent resection after neoadjuvant chemotherapy. Therefore, a more comprehensive pathologic evaluation is warranted in these patients.

Metabolic tumor constitution is superior to tumor regression grading for evaluating response to neoadjuvant therapy of esophageal adenocarcinoma patients.

The response to neoadjuvant therapy can vary widely between individual patients. Histopathological tumor regression grading (TRG) is a strong factor for treatment response and survival prognosis of esophageal adenocarcinoma (EAC) patients following neoadjuvant treatment and surgery. However, TRG systems are usually based on the estimation of residual tumor but do not consider stromal or metabolic changes after treatment. Spatial metabolomics analysis is a powerful tool for molecular tissue phenotyping but has not been used so far in the context of neoadjuvant treatment of esophageal cancer. We used imaging mass spectrometry to assess the potential of spatial metabolomics on tumor and stroma tissue for evaluating therapy response of neoadjuvant-treated EAC patients. With an accuracy of 89.7%, the binary classifier trained on spatial tumor metabolite data proved to be superior for stratifying patients when compared with histopathological response assessment, which had an accuracy of 70.5%. Sensitivities and specificities for the poor and favorable survival patient groups ranged from 84.9% to 93.3% using the metabolic classifier and from 62.2% to 78.1% using TRG. The tumor classifier was the only significant prognostic factor (HR 3.38, 95% CI 1.40-8.12, p = 0.007) when adjusted for clinicopathological parameters such as TRG (HR 1.01, 95% CI 0.67-1.53, p = 0.968) or stromal classifier (HR 1.86, 95% CI 0.81-4.25, p = 0.143). The classifier even allowed us to further stratify patients within the TRG1-3 categories. The underlying mechanisms of response to treatment have been figured out through network analysis. In summary, metabolic response evaluation outperformed histopathological response evaluation in our study with regard to prognostic stratification. This finding indicates that the metabolic constitution of the tumor may have a greater impact on patient survival than the quantity of residual tumor cells or the stroma. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

[Grading of tumor regression of gastrointestinal carcinomas after neoadjuvant therapy]. / Grading der Tumorregression gastrointestinaler Karzinome nach neoadjuvanter Therapie.

Pre- or perioperative chemo- or radiochemotherapy and subsequent resection is the standard therapy for locally advanced esophageal, gastric, and rectal cancer. A tumor regression grading (TRG; also tumor regression grade) categorizes the extent of the regressive changes after a neoadjuvant treatment. There are several TRG systems for gastrointestinal carcinomas that relate either to the extent of the therapy-induced fibrosis in relation to the residual tumor or the estimated proportion of the residual tumor in the area of the former tumor area. An ideal TRG system shows significant interobserver agreement and offers relevant prognostic information - in most cases a complete or almost complete regression after neoadjuvant therapy is associated with an improved prognosis. In this review, the most commonly used TRG systems for gastrointestinal carcinomas are presented and discussed. In addition, current issues such as the standardization of TRG and the subject of regression in lymph node metastases in the context of a TRG system are discussed.

[Complete response after neoadjuvant therapy : How certain is the pathology?] / Komplettresponse nach neoadjuvanter Therapie : Wie sicher ist die Pathologie?

Histopathologic evaluation of tumors after neoadjuvant therapy is performed by tumor regression grading (TRG) systems, which reflect the proportion of vital residual primary tumor in relation to the previous total tumor. The World Health Organization (WHO) tumor grading is replaced by TRG in tumor classification. The histopathological work-up of a tumor is based on the criteria of the TNM classification even after neoadjuvant therapy. A uniform TRG does not exist. For various tumors TRGs based on the tumor entity have been established, consisting of a 3-stage or 5­stage grading system. Complete histopathological tumor regression is only present if no vital tumor cells are detectable in the histopathological examination of the primary surgical specimens (primary tumor and accompanying locoregional lymph nodes) and there are no distant metastases.

Rectal tumor fragmentation as a response pattern following chemoradiation.

Background: Tumor response to neoadjuvant therapy is heterogenous and prognostically important for locally advanced rectal adenocarcinoma (LARC) patients. Commonly applied response classification approaches including tumor regression grading (TRG) and TN downstaging can be discordant. The aim of this study is to compare the prognostic value of discordant tumor response measurement categorized according to the AJCC/CAP TRG schema and ypTN stage. Methods: This is a single-center retrospective review of 90 consecutive patients with stage II-III rectal cancer receiving neoadjuvant chemoradiation (nCRT), total mesorectal excision (TME) and adjuvant chemotherapy (ACT) between 2007 and 2018. Two pathologists re-examined each case to assign a consensus AJCC TRG. A Cox proportional hazards ratio model assessed the effect of patient, tumor, and treatment factors on disease-free survival (DFS). Results: Median follow-up after surgery was 46 months (95% CI: 41-50 months). Median age at diagnosis was 55 years (range: 27-80). Most patients were male (58%) and Caucasian (92%) with clinical stage III disease (68%). Seventy-three patients (81%) underwent low anterior resection (LAR), 17 (19%) underwent abdominoperineal resection (APR). The median interval from completion of nCRT to surgery was 62 days (IQR: 56-70 days). The 4-year OS, DFS, and LC was 92.4%, 74.4%, and 90.2%, respectively. In the multivariate analysis, ypTN downstaging was not prognostically significant; however, AJCC TRG score 3 (minimal tumor response to treatment) was strongly predictive for inferior DFS (3-year DFS 79% vs. 25%, P<0.001). Patients with TRG 3 had a significantly higher risk of both local (75% vs. 5%) and distant failure (75% vs. 19%). Conclusions: Minimal tumor response to neoadjuvant therapy, AJCC TRG 3, irrespective of ypTN downstaging, is a pattern of residual disease that is at highest risk for recurrence. Response categorization discrepancies may be partly explained by alternative patterns of residual disease, including tumor fragmentation, and may be best reflected by TRG. The optimal tumor response categorization method requires further study to best stratify patient risk and management.

Prognostic Value of Tumor Regression Grading in Patients Treated With Neoadjuvant Chemotherapy Plus Surgery for Gastric Cancer.

OBJECTIVE: To validate the prognostic value of tumor regression grading (TRG) and to explore the associated factors of TRG for advanced gastric cancer (AGC) with neoadjuvant chemotherapy (NACT) plus surgery. METHODS: Two hundred forty-nine AGC patients treated with NACT followed by gastrectomy at the Mayo Clinic, USA and the Fujian Medical University Union Hospital, China between January 2000 and December 2016 were enrolled in this study. Cox regression was used to identify covariates associated with overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to reveal factors predicting tumor regression grading. RESULTS: For patients with TRG 0-1, the 3- and 5-year OS rates were 85.2% and 74.5%, respectively, when compared to 56.1% and 44.1% in patients with TRG 2 and 28.2% and 23.0% in patients with TRG 3, respectively (p<0.001). TRGs were independent risk factors for OS. Similar findings were observed in RFS. Multivariable analysis revealed that an oxaliplatin-based regimen (p=0.017) was an independent predictor of TRG. The oxaliplatin-based regimen was superior to the nonoxaliplatin-based regimen for OS (38.4 months vs 19.5 months, respectively; p=0.01). Subgroup analyses by histological subtype indicated that the oxaliplatin-based regimen improved the OS in nonsignet ring cell carcinoma compared to the nonoxaliplatin-based regimen (53.7 months vs 19.5 months, respectively; p=0.011). However, similar findings were not observed in RFS. CONCLUSION: TRG was an independent factor of AGC treated with neoadjuvant chemotherapy plus surgery. Oxaliplatin-based neoadjuvant chemotherapy regimens improve tumor response and may have an overall survival benefit for patients with nonsignet ring cell carcinoma.

Neoadjuvant Chemoradiation Combined with Regional Hyperthermia in Locally Advanced or Recurrent Rectal Cancer.

BACKGROUND: To prospectively analyze feasibility and pathological complete response (pCR) rates of neoadjuvant chemoradiotherapy combined with regional hyperthermia (RHT) in patients with locally advanced (LARC) or recurrent (LRRC) rectal cancer. METHODS: between 2012 and 2018, 111 patients with UICC stage IIB-IV or any locally recurrent rectal cancer were included (HyRec-Trial, ClinicalTrials.gov Identifier: NCT01716949). Patients received radiotherapy with concurrent 5-Fluororuracil (5-FU)/Capecitabine and Oxaliplatin, and RHT. Stage 1 feasibility analysis evaluated dose-limiting toxicities (DLT) after 19 patients, stage 2 after 59 evaluable patients. Analysis of the pCR rate was based on histopathological reports. RESULTS: the feasibility rates for stages 1 and 2 were 90% (17/19) and 73% (43/59), respectively. In the intention-to-treat population the pCR rate was 19% (20/105; 90% confidence interval (CI) 13.0-26.5). In the per-protocol-analysis, complete tumor regression was seen in 28% (18/64) and 38% (3/8) of the patients with LARC and LRRC, respectively. Complete resection rates (R0) among patients with LARC and LRRC who received surgery were 99% (78/84) and 67% (8/12). CONCLUSIONS: the intensified neoadjuvant and multimodality treatment schedule was feasible and led to comparable early toxicity rates as described by other trials that used the similar chemoradiation protocol. The presented treatment regimen resulted in a very high pCR rate and appears as a promising option for patients with LRRC.

Intracellular Nampt impairs esophageal squamous cell carcinoma neo-adjuvant chemotherapy response independent of eNampt.

Nampt consists of iNampt and eNampt, might contribute to modulating obesity-related malignancies and impairing response to chemotherapy in a range of cancers. This study explored the role of Nampt and adiposity in the progression and response to neo-adjuvant chemotherapy of esophageal squamous cell carcinoma (ESCC). Patients with ESCC were treated with 2 cycles of neo-adjuvant chemotherapy, then evaluated for surgery. Tumor regression grading (TRG) and prognosis of these patients were collected. Anthropometry was well utilized. Serum eNampt was determined by enzyme-linked immunosorbent assay, iNampt expression in tissues were assessed by PCR, western blot and immunohistochemistry. eNampt in sera elevated significantly in these over-weight or obese patients, and was positively associated with body mass index (BMI), waist circumference, visceral fat area (VFA), subcutaneous fat area (SFA) and total fat area (TFA) (P<0.05). iNampt expression in the mRNA and protein levels were up-regulated in ESCC compared to their adjacent non-tumor specimens (P<0.05). iNampt protein staining revealed mainly in the cytoplasm and nuclei, while it was not related to serum eNampt, BMI, waist circumference, VFA, SFA and TFA (P>0.05). Pre-treatment iNampt, BMI, SFA, TFA and age significantly correlated with neo-adjuvant chemotherapy response, and iNampt expression and age were independent predictors (P<0.05). Pre-treatment iNampt, ypT, ypN, ypTNM stage and TRG were associated with the survival of ESCCs, and ypN stage and TRG were independent prognostic factors (P<0.05). In conclusion, iNampt impaired ESCC response to neo-adjuvant chemotherapy independent of eNampt, targeting iNampt to increase ESCC response to neo-adjuvant chemotherapy would improve the prognosis of ESCCs.

[Predictive value of combination of MRI tumor regression grade and apparent diffusion coefficient for pathological complete remission after neoadjuvant treatment of locally advanced rectal cancer].

Objective: Pelvic high-resolution magnetic resonance imaging (MRI) has now become a standard method for evaluating the efficacy of neoadjuvant treatment for locally advanced rectal cancer (LARC). However, this traditional morphological qualitative assessment method based on T2-weighted imaging (T2WI) is not effective in predicting pathological complete remission (pCR). The purpose of this study is to investigate whether combining the magnetic resonance tumor regression grade (mrTRG) with apparent diffusion coefficient (ADC) can improve diagnostic value for pCR after preoperative neoadjuvant chemoradiotherapy (nCRT) of LARC. Methods: This was a diagnostic study. Clinicopathological data of 134 LARC patients who received nCRT and radical surgery in the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2019 were retrospectively analyzed. All the patients underwent MRI which included T2WI and DWI sequences before and 8 weeks after nCRT. Two radiologists independently drew ROIs on T2WI and DWI to estimate mrTRG stage and calculate the mean ADC value. Receiver operating characteristics (ROC) method was applied to evaluate the predict value of mrTRG combined with mean ADC value for pCR. Results: Of 134 LARC patients, 85 were male and 49 were female with median age of 58 (28-82) years. After nCRT, MRI suggested 21 patients (15.7%) had clinical complete remission (cCR), e.g. mrTRG stage 1-2. Postoperative pathology revealed 31 (23.1%) patients had pCR. The evaluations of mrTRG and ADC value by the two readers were highly consistent, and the intra-group correlation coefficients were 0.83 (95% CI: 0.703-0.881) and 0.96 (95% CI: 0.989-0.996), respectively. There was a negative correlation between mrTRG and pCR (r(s)=-0.505, P<0.01), and a positive correlation between mean ADC value and pCR (r(s)=0.693, P<0.01). The ROC curve showed that mrTRG alone had a medium predictive value for pCR, with an area under the curve (AUC) of 0.832 (95% CI: 0.743-0.921); the mean ADC value had a higher predictive value for pCR, with AUC of 0.906 (95% CI: 0.869-0.962). The predictive value of the combined model of mrTRG and ADC value for pCR was significantly better than that of mrTRG alone (P=0.015), and the AUC was 0.908 (95% CI: 0.849-0.968). Conclusion: Both mrTRG and mean ADC value can be non-invasive methods to predict the efficacy of nCRT for LARC. Combining the mean ADC value with mrTRG can result in better pCR prediction.

Prognostic assessment of resected colorectal liver metastases integrating pathological features, RAS mutation and Immunoscore.

Surgical resection of colorectal liver metastases combined with systemic treatment aims to maximize patient survival. However, recurrence rates are very high postsurgery. In order to assess patient prognosis after metastasis resection, we evaluated the main patho-molecular and immune parameters of all surgical specimens. Two hundred twenty-one patients who underwent, after different preoperative treatment, curative resection of 582 metastases were analyzed. Clinicopathological parameters, RAS tumor mutation, and the consensus Immunoscore (I) were assessed for all patients. Overall survival (OS) and time to relapse (TTR) were estimated using the Kaplan-Meier method and compared by log-rank tests. Cox proportional hazard models were used for uni- and multivariate analysis. Immunoscore and clinicopathological parameters (number of metastases, surgical margin, histopathological growth pattern, and steatohepatitis) were associated with relapse in multivariate analysis. Overall, pathological score (PS) that combines relevant clinicopathological factors for relapse, and I, were prognostic for TTR (2-year TTR rate PS 0-1: 49.8.% (95% CI: 42.2-58.8) versus PS 2-4: 20.9% (95% CI: 13.4-32.8), hazard ratio (HR) = 2.54 (95% CI: 1.82-3.53), p < 0.0000; and 2-year TTR rate I 0: 25.7% (95% CI: 16.3-40.5) versus I 3-4: 60% (95% CI: 47.2-76.3), HR = 2.87 (95% CI: 1.73-4.75), p = 0.0000). Immunoscore was also prognostic for OS (HR [I 3-4 versus I 0] = 4.25, 95% CI: 1.95-9.23; p = 0.0001). Immunoscore (HR [I 3-4 versus I 0] = 0.27, 95% CI: 0.12-0.58; p = 0.0009) and RAS mutation (HR [mutated versus WT] = 1.66, 95% CI: 1.06-2.58; p = 0.0265) were significant for OS. In conclusion, PS including relevant clinicopathological parameters and Immunoscore permit stratification of stage IV colorectal cancer patient prognosis in terms of TTR and identify patients with higher risk of recurrence. Immunoscore remains the major prognostic factor for OS.

Predictive value of combination of MRI tumor regression grade and apparent diffusion coefficient for pathological complete remission after neoadjuvant treatment of locally advanced rectal cancer / 中华胃肠外科杂志

Objective: Pelvic high-resolution magnetic resonance imaging (MRI) has now become a standard method for evaluating the efficacy of neoadjuvant treatment for locally advanced rectal cancer (LARC). However, this traditional morphological qualitative assessment method based on T2-weighted imaging (T2WI) is not effective in predicting pathological complete remission (pCR). The purpose of this study is to investigate whether combining the magnetic resonance tumor regression grade (mrTRG) with apparent diffusion coefficient (ADC) can improve diagnostic value for pCR after preoperative neoadjuvant chemoradiotherapy (nCRT) of LARC. Methods: This was a diagnostic study. Clinicopathological data of 134 LARC patients who received nCRT and radical surgery in the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2019 were retrospectively analyzed. All the patients underwent MRI which included T2WI and DWI sequences before and 8 weeks after nCRT. Two radiologists independently drew ROIs on T2WI and DWI to estimate mrTRG stage and calculate the mean ADC value. Receiver operating characteristics (ROC) method was applied to evaluate the predict value of mrTRG combined with mean ADC value for pCR. Results: Of 134 LARC patients, 85 were male and 49 were female with median age of 58 (28-82) years. After nCRT, MRI suggested 21 patients (15.7%) had clinical complete remission (cCR), e.g. mrTRG stage 1-2. Postoperative pathology revealed 31 (23.1%) patients had pCR. The evaluations of mrTRG and ADC value by the two readers were highly consistent, and the intra-group correlation coefficients were 0.83 (95% CI: 0.703-0.881) and 0.96 (95% CI: 0.989-0.996), respectively. There was a negative correlation between mrTRG and pCR (r(s)=-0.505, P<0.01), and a positive correlation between mean ADC value and pCR (r(s)=0.693, P<0.01). The ROC curve showed that mrTRG alone had a medium predictive value for pCR, with an area under the curve (AUC) of 0.832 (95% CI: 0.743-0.921); the mean ADC value had a higher predictive value for pCR, with AUC of 0.906 (95% CI: 0.869-0.962). The predictive value of the combined model of mrTRG and ADC value for pCR was significantly better than that of mrTRG alone (P=0.015), and the AUC was 0.908 (95% CI: 0.849-0.968). Conclusion: Both mrTRG and mean ADC value can be non-invasive methods to predict the efficacy of nCRT for LARC. Combining the mean ADC value with mrTRG can result in better pCR prediction.